Lysine acetylation mediates protein interactions in gene transcription. It is modulated by specific bromodomains (BRDs), which bind acetyl-lysine and are found in transcriptional co-activators with histone acetyltransferase activity such as CBP (CREB-binding protein) and chromatin-associating proteins. Bromodomain/acetyl-lysine binding is important for CBP acetyltransferase activity on biological targets, and for the recruitment of transcriptional proteins and enzymes affecting histone acetylation during gene activation. Previous studies have shown that lineage progression of progenitors towards myelinating oligodendrocytes is correlated with increased chromatin compaction and histone deacetylation. Oligodendrocytes are glial cells in the central nervous system, whose membrane forms the insulating coating termed myelin that wraps the axons and allows fast axonal conduction. Improper progenitor differentiation or myelin formation is detected in various neurological disorders.
In addition, transcriptional co-activators CREB-binding protein (CBP) and p300 (also known as KAT3B and KAT3A, respectively) play a central role in regulating p53 stability and its function as a transcription factor in response to genotoxic stress. Like histones, lysine acetylation of transcription factors facilitates the recruitment of BRD-containing cofactors required for chromatin structural change and transcriptional initiation and elongation. The biochemical contribution of acetylation to p53 transcription functions has been attributed to nuclear translocation, alteration of DNA binding ability and enhancement of transcriptional potential. p53 acetylation plays an important part in promoting molecular interactions with transcriptional co-regulators leading to target gene activation that ultimately determines cellular responses to stress in the forms of senescence, cell growth arrest, or apoptosis.